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Eur J Obstet Gynecol Reprod Biol. 2014 May;176:68-74. doi: 10.1016/j.ejogrb.2014.02.036. Epub 2014 Mar 4.

Association of CYP1A1 gene variants rs4646903 (T>C) and rs1048943 (A>G) with cervical cancer in a North Indian population.

Author information

1
Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, Uttar Pradesh, India. Electronic address: rizvi.109@gmail.com.
2
Department of Radiotherapy, King George's Medical University, Lucknow 226003, Uttar Pradesh, India. Electronic address: drkirtis@rediffmail.com.
3
Department of Microbiology, Integral University, Lucknow 226026, Uttar Pradesh, India. Electronic address: imranmohdkhan@rediffmail.com.
4
Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, Uttar Pradesh, India. Electronic address: banerjee_monisha30@rediffmail.com.

Abstract

OBJECTIVE:

To evaluate the association of CYP1A1 gene polymorphisms with cervical cancer susceptibility in general and in relation to tobacco smoking.

STUDY DESIGN:

The study included 408 subjects from North India (208 controls and 200 cases). All subjects were genotyped for CYP1A1 m1 T>C (rs4646903) and m2 A>G (rs1048943) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by statistical analysis (SPSS, version 15.0; SHEsis online version).

RESULTS:

In our population, individuals with TC and CC genotypes of CYP1A1 m1 polymorphism have significantly higher risk of cervical cancer (adjusted odds (OR) 2.76, P=0.001; 3.13, P=0.006 respectively). In the case of m2 polymorphism, individuals with AG and GG genotypes show increased risk of cervical cancer (OR 1.90, P=0.021; and 3.05, P=0.285 respectively). The 'C' allele of m1 and 'G' allele of m2 polymorphism were strongly associated with the disease (P<0.0001 and 0.008 respectively). Multiple combinations showed that women carrying the genotypes viz. TC/AA (+/-), TC/AG (+/+), CC/AG (-/+) and CC/AG (+/+) were at higher risk of developing cervical cancer. The relationship between CYP1A1 m1 and m2 genotypes and tobacco smoking showed an 8-11-fold higher risk of cervical cancer amongst active smokers and 3-4-fold in passive smokers as well. Linkage disequilibrium between m1 and m2 showed highly significant association in the case of TA* (P<0.0001) haplotype, while 'CG' appeared to be the risk haplotype (P=0.002).

CONCLUSION:

Our results suggest that presence of the 'C' allele of m1 (T>C) and 'G' of m2 (A>G) may be the risk alleles for cervical cancer susceptibility. Moreover, CYP1A1 m1 and m2 polymorphisms show considerable association with tobacco smoking in our study population.

KEYWORDS:

CYP1A1; Cervical cancer; North India; PCR-RFLP; SNP

PMID:
24657182
DOI:
10.1016/j.ejogrb.2014.02.036
[Indexed for MEDLINE]

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